For all senses except olfaction, the thalamus is the primary source of cortical input and is involved in many functions ranging from basic sensory information processing, to more complex functions such as sensory gating or attention modulation. Although there is no thalamic relay between the olfactory sensory neurons and the olfactory cortex (piriform cortex), there is a direct projection from the piriform cortex (PCX) to he mediodorsal thalamic nucleus (MDT) and the MDT projects in turn to the orbitofrontal cortex (OFC). Lesion studies and recent functional magnetic resonance imaging studies in humans suggest that the MDT may be particularly important in odor attention, rather than in odor discrimination per se. Based on its crossroad location between PCX and OFC and its specific activation during odor attention processes in humans, I hypothesize that the MDT is involved in, and required for odor attention processes. In this R03 proposal, I propose multi-disciplinary approaches combining electrophysiological, behavioral, and optogenetic techniques to test this hypothesis. Aim 1 is to test the hypothesis that 1) MDT neurons are active during tasks requiring attention to odors, notably when the attention demand is high and 2) MDT functional connectivity with PCX and/or OFC will be differentially modulated depending on the odor attention level of the task. To explore this question, I will use simultaneous multiple-regional electrophysiological recordings (local field potential and single unit activity) in behaving rats during an innovative odor attention task. Aim 2 is to test the sensory component of MDT activity in an odor attention requiring task. I will use optogenetic tools to selectively inhibit PCX output neuron axons targeting the MDT and simultaneously record MDT activity and behavior during the olfactory attention task. Aim 3 is to test whether and when MDT activity is required in the odor attention task. I will use optogenetic tools to selectively and temporally inhibit CAMKII expressing MDT output neuron activity during specific behaviorally defined phases of odor attention trials. The results of the present proposal will further our understanding of the enigmatic role of thalamus in odor coding and will give access to the mechanisms underlying attention in a unique sensory modality.